Hemoglobin: Structure, Function, and Types Explained

Understanding Hemoglobin

Hemoglobin (Hb) is a blood heteroprotein with a molecular weight of 64,000 (64 kDa). This characteristic red pigment transports oxygen from respiratory organs to tissues in mammals, oviparous animals, and other species.

Hemoglobin changes color based on oxygenation: it turns a bright scarlet red when bound to oxygen (arterial blood) and a dark red when oxygen is released (venous blood).

Structure of the Heme Group

Hemoglobin consists of four polypeptide chains (globins), each bound to a heme group containing an iron atom that binds reversibly to oxygen. The heme group is formed through the following process:

1. Synthesis: Succinyl CoA (from the Krebs cycle) joins with glycine to form a pyrrole group.
2. Protoporphyrin Formation: Four pyrrole groups combine to form protoporphyrin IX.
3. Iron Binding: Protoporphyrin IX binds to a ferrous iron molecule (Fe2+) to form the final heme group.

Types of Hemoglobin

• Hemoglobin A (HbA): Known as adult or normal hemoglobin, it represents approximately 97% of hemoglobin in adults and consists of two alpha and two beta globins.
• Hemoglobin A2: Comprises less than 2.5% of hemoglobin after birth. It consists of two alpha and two delta globins; levels increase significantly in beta-thalassemia when beta-globin synthesis is impaired.
• Hemoglobin S: A genetic variant associated with Sickle Cell Anemia, predominantly affecting African American and Native American populations.
• Hemoglobin F: The primary form of fetal hemoglobin.
• Oxyhemoglobin: Hemoglobin bound to oxygen (Hb + O₂).
• Methemoglobin: Hemoglobin with iron in the ferric state (Fe3+). It cannot bind oxygen and is caused by congenital methemoglobin reductase deficiency or exposure to oxidizing agents like nitrites.
• Carbaminohemoglobin: Hemoglobin bound to CO₂ following gas exchange between blood cells and tissues (Hb + CO₂).
• Carboxyhemoglobin: Formed by the union of hemoglobin with carbon monoxide (CO). Because CO has an affinity for Hb 200 times greater than oxygen, it causes tissue hypoxia and can be lethal at high concentrations (40%).
• Glycated Hemoglobin: Formed by the binding of Hb with free carbohydrates; it is a key clinical marker in diabetes management.